The lifetime risk of colorectal cancer is over 5% in the United States where, despite recent declines in incidence and mortality, colorectal cancer remains the second highest cause of cancer death. Better treatments have improved survival rates, but morbidity and mortality could be more rapidly and cost-effectively reduced by achieving higher uptake and long-term adherence to colorectal cancer screening. The Systems of Support to Decrease Colorectal Cancer (SOS) study successfully advanced colorectal screening. SOS was a 4-arm randomized controlled trial that leveraged electronic health record data and automated systems to implement stepwise increases in screening support. Patients due for screening (n=4675) were randomized to (1) Usual Care, (2) Automated care (automated mailings and fecal occult blood tests), (3) automated plus assisted care from medical assistants (phone reminders and sending orders to physicians to sign), or (4) automated + assisted + navigated care from registered nurses (follow-up until test completion). Interventions were repeated in year 2. Compared to usual care, intervention patients were more likely to be current for colorectal cancer screening in both study years, with increases by intervention intensity: Usual Care 26.5%, Automated 50.7%, Assisted 57.7%, and Navigated 64.4% (P<.001). We propose to improve and continue SOS interventions up to 10 years and measure their effects on long-term adherence and outcomes. We will: 1. Identify factors related to low or non-adherence to screening despite receiving continued interventions and apply these findings to a stepped intervention to increase uptake and long-term adherence of screening. 2. Assess the effectiveness of the SOS interventions on long-term screening adherence up to 10 years. 3. Describe the impact of SOS interventions on colorectal cancer-related costs and clinical outcomes.